Evidence from case-control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity.
Abstract
In this study, we investigated 102 single-nucleotide polymorphisms (SNPs) covering
the common genetic variation in 16 genes recurrently regarded as candidates for human
longevity: APOE; ACE; CETP; HFE; IL6; IL6R; MTHFR; TGFB1; APOA4; APOC3; SIRTs 1, 3,
6; and HSPAs 1A, 1L, 14. In a case-control study of 1,089 oldest-old (ages 92-93)
and 736 middle-aged Danes, the minor allele frequency (MAF) of rs769449 (APOE) was
significantly decreased in the oldest-old, while the MAF of rs9923854 (CETP) was significantly
enriched. These effects were supported when investigating 1,613 oldest-old (ages 95-110)
and 1,104 middle-aged Germans. rs769449 was in modest linkage equilibrium (R (2)=0.55)
with rs429358 of the APOE-ε4 haplotype and adjusting for rs429358 eliminated the association
of rs769449, indicating that the association likely reflects the well-known effect
of rs429358. Gene-based analysis confirmed the effects of variation in APOE and CETP
and furthermore pointed to HSPA14 as a longevity gene. In a longitudinal study with
11 years of follow-up on survival in the oldest-old Danes, only one SNP, rs2069827
(IL6), was borderline significantly associated with survival from age 92 (P-corrected=0.064).
This advantageous effect of the minor allele was supported when investigating a Dutch
longitudinal cohort (N=563) of oldest-old (age 85+). Since rs2069827 was located in
a putative transcription factor binding site, quantitative RNA expression studies
were conducted. However, no difference in IL6 expression was observed between rs2069827
genotype groups. In conclusion, we here support and expand the evidence suggesting
that genetic variation in APOE, CETP, and IL6, and possible HSPA14, is associated
with human longevity.
Type
Journal articleSubject
Aged, 80 and overAlleles
Apolipoproteins E
Case-Control Studies
Cholesterol Ester Transfer Proteins
Denmark
Female
Gene Frequency
Genetic Variation
Genotype
Germany
Haplotypes
Humans
Interleukin-6
Linear Models
Longevity
Longitudinal Studies
Male
Middle Aged
Netherlands
Polymorphism, Single Nucleotide
Registries
Permalink
https://hdl.handle.net/10161/14777Published Version (Please cite this version)
10.1007/s11357-011-9373-7Publication Info
Soerensen, Mette; Dato, Serena; Tan, Qihua; Thinggaard, Mikael; Kleindorp, Rabea;
Beekman, Marian; ... Christiansen, Lene (2013). Evidence from case-control and longitudinal studies supports associations of genetic
variation in APOE, CETP, and IL6 with human longevity. Age (Dordr), 35(2). pp. 487-500. 10.1007/s11357-011-9373-7. Retrieved from https://hdl.handle.net/10161/14777.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
Collections
More Info
Show full item recordScholars@Duke
James Walton Vaupel
Research Professor in the Sanford School of Public Policy

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy
Rights for Collection: Scholarly Articles